Oxygen-Ozone Therapy for the Treatment of Knee Osteoarthritis: A Systematic Review of Randomized Controlled Trials

Purpose: To review the available literature on the application of oxygen-ozone therapy (OOT) in the treatment of knee osteoarthritis (KOA) to understand its therapeutic potential and to compare it with other conservative treatment options. Methods: A systematic review of the literature was performed on the PubMed, Cochrane, Embase, ResearchGate, and PedRo Databases, with the following inclusion criteria: (1) randomized controlled trials (RCT5), (2) written in English, (3) published on indexed journals in the last 20 years (1998-2018), (4) dealing with the use of ozone intra-articular injection for the treatment of KOA. The risk of bias was assessed by the Cochrane Risk of Bias tool for RCT5. Results: Eleven studies involving 858 patients in total (629 female and 229 male) were included. Patients in the control groups received different treatments: placebo in 1 trial; hyaluronic acid in 2 studies; hyaluronic acid and PRP in 1 trial; corticosteroids in 4; and hypertonic dextrose, radiofrequency, or celecoxib + glucosamine in the remaining 3 trials. In looking at the quality of the available literature, we found that none of the studies included reached "good quality" standard, 2 were ranked as "fair," and the rest were considered "poor." No major complications or serious adverse events were reported following intraarticular OOT, which provided encouraging pain relief at short term. On the basis of the available data, no clear indication emerged from the comparison of OOT with other established treatments for KOA. Conclusions: The analysis of the available RCT5 on OOT for KOA revealed poor methodologic quality, with most studies flawed by relevant bias, thus severely limiting the possibility of drawing conclusions on the efficacy of OOT compared with other treatments. On the basis of the data available, OOT has, however, proven to be a safe approach with encouraging effects in pain control and functional recovery in the short-middle term.